Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Impact of bidirectional signaling between megakaryocytes and osteosarcoma cells on metastasis

Award Number: F32CA284698
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/15/2024
PERIOD OF PERFORMANCE END DATE: 05/14/2027

Group Awards By:

View Award Description

Impact of bidirectional signaling between megakaryocytes and osteosarcoma cells on metastasis - PROJECT ABSTRACT: Osteosarcoma (OS) is the most common primary bone malignancy worldwide and primarily affects adolescents. While the 5-year survival rate is around 70% with localized disease, metastatic disease survival remains a dismal 20% with little improvement over past years. It is recognized that interactions within the microenvironment can either facilitate or inhibit cancer cell metastasis, thus a deeper analysis of these interactions may identify targetable vulnerabilities of metastatic OS. Previous studies by our lab and others have shown that platelets promote metastasis of several types of cancer. In contrast, the role of megakaryocytes (MKs), platelet producing cells, in cancer metastasis has not been established. While MKs are primarily recognized as platelet producers, they also serve as dynamic regulators of bone production that both influence and are influenced by bone cells. A previous study found that co-culture of OS cells with MKs increased OS proliferation suggesting that MKs could influence OS cells within the bone microenvironment Additionally, a study found that breast cancer tumor bearing mice displayed altered MK polyploidy and increased platelet RNA and protein content demonstrating that tumors can influence MK function and alter the produced platelets. My preliminary data suggests that platelet depletion in mice decreases initial lung seeding of OS cells administered via tail vein. My preliminary data also shows increased MKs but decreased MK ploidy in mice with orthotopic OS tumors. Based on these previous studies and my preliminary data, I hypothesize that OS and MK bidirectional signaling contributes to OS progression and metastasis by exchanging signaling mediators that lead to alterations in MK differentiation, maturation, platelet production and function, while also increasing OS cell proliferation and migration in the primary tumor. To study this mechanism, I will use a novel tibial implantation technique to establish orthotopic primary tumors in both wild-type and MK-depletion mice (PF4CreiDTR mice). I will use this approach to test the following specific aims: Aim 1 is to test the hypothesis that OS primary tumors dysregulate MK differentiation and maturation leading to altered platelet proteome content. and function. I will perform the tibial implant procedure or a sham procedure on WT mice and compare bone marrow MK maturation and differentiation via flow cytometry across three time points to evaluate changes in MKs throughout OS tumor progression. I will assess platelet function and activation from both groups via aggregometry and flow cytometry. Finally changes in MK transcriptome and platelet proteome will be compared between groups. Aim 2 is to test the hypothesis that MK-OS interactions during primary OS tumor development promote OS cell proliferation and metastasis. I will deplete MKs in OS tumor bearing mice and examine how tumor growth, proliferation, lung metastasis, and the tumor transcriptome compare to wild-type (WT) mice. The results of these experiments will reveal how OS-MK interactions affect OS metastasis and identify candidate mediators for future study of the mechanisms involved and of their potential as therapeutic targets.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $78,040 )
2025	2025	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Research Manpower	000	2	7/3/2025	NON-COMPETING CONTINUATION	$78,040
														Subtotal = $78,040

Issue Date FY: 2024 ( Subtotal = $74,284 )
2024	2024	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Research Manpower	000	1	3/20/2024	NEW	$69,500
2024	2024	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Research Manpower	002	1	5/7/2024	NEW	$0
2024	2024	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Research Manpower	001	1	5/7/2024	NEW	$4,784
														Subtotal = $74,284

Grand Total All Awards = $152,324

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Impact of bidirectional signaling between megakaryocytes and osteosarcoma cells on metastasis

Award Number: F32CA284698

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/15/2024

PERIOD OF PERFORMANCE END DATE: 05/14/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer